These studies propose to examine: 1) regulation of segmental resistance of cerebral arteries, 2) effects of peripheral sympathetic and cholinergic nerves on cerebral blood flow (CBF), and 3) role of central brain pathways in regulation of CBF. The cerebral circulation is unique in that both large and small arteries participate actively in the regulation of cerebrovascular resistance. I will determine whether different vascular segments respond preferentially to changes in arterial pressure and to stimulation of sympathetic nerves. Cerebral vessels are richly innervated by sympathetic nerves but the functional significance of this innervation is unclear. I will determine if sympathetic pathways to cerebral vessels are reflexly activated during hypertension in awake rabbits and have significant effects on CBF. Although cerebral vessels receive innervation from cholinergic nerves, the source of this innervation is unclear. Studies are proposed to determine whether cholinergic nerves reach cerebral vessels via the greater superficial petrosal nerve, a branch of the facial nerve. Anatomical and physiological evidence suggest that there is a functional interaction between sympathetic and cholinergic nerves supplying cerbral vessels. I will investigate whether stimulation of cholinergic nerves attenuates constrictor effects of sympathetic nerves on CBF. Central cholinergic pathways may become activated during hypercapnia and participate in dilation of cerebral vessels. Studies are proposed to determine whether atropine attenuates vasodilation of cerebral vessels during hypercapnia. It has been suggested that cerebral vessels receive innervation via central brain pathways which are independent of peripheral neural pathways. I will determine whether activation of these pathways have direct effects on CBF, or alter CBF secondarily to changes in cerebral metabolism. These proposed studies are intended to provide new information concerning the regulation of the cerebral circulation.